title: A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation.
abstract: The nonrandom distribution of meiotic recombination influences patterns of inheritance and genome evolution, but chromosomal features governing this distribution are poorly understood. Formation of the DNA double-strand breaks (DSBs) that initiate recombination results in the accumulation of Spo11 protein covalently bound to small DNA fragments. By sequencing these fragments, we uncover a genome-wide DSB map of unprecedented resolution and sensitivity. We use this map to explore how DSB distribution is influenced by large-scale chromosome structures, chromatin, transcription factors, and local sequence composition. Our analysis offers mechanistic insight into DSB formation and early processing steps, supporting the view that the recombination terrain is molded by combinatorial and hierarchical interaction of factors that work on widely different size scales. This map illuminates the occurrence of DSBs in repetitive DNA elements, repair of which can lead to chromosomal rearrangements. We also discuss implications for evolutionary dynamics of recombination hot spots.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Mariko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Ryan
authors.initials: R
authors.lastname: Kniewel
authors.forename: Hajime
authors.initials: H
authors.lastname: Murakami
authors.forename: Hannah G
authors.initials: HG
authors.lastname: Blitzblau
authors.forename: Sam E
authors.initials: SE
authors.lastname: Tischfield
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Neale
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochwagen
authors.forename: Scott
authors.initials: S
authors.lastname: Keeney
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004706:Endodeoxyribonucleases / Q000378:metabolism; D016681:Genome, Fungal; D055106:Genome-Wide Association Study; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D004706:Endodeoxyribonucleases; D029701:Saccharomyces cerevisiae Proteins; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11